Dampness and mold in homes across China: Associations with rhinitis, ocular, throat and dermal symptoms, headache and fatigue among adults.

We studied dampness and mold in China in relation to rhinitis, ocular, throat and dermal symptoms, headache and fatigue. A questionnaire study was performed in six cities including 36 541 randomized parents of young children. Seven self-reported signs of dampness were evaluated. Multilevel logistic regression models were used to calculate odds ratios (ORs). Totally, 3.1% had weekly rhinitis, 2.8% eye, 4.1% throat and 4.8% skin symptoms, 3.0% headache and 13.9% fatigue. Overall, 6.3% of the homes had mold, 11.1% damp stains, 35.3% damp bed clothing, 12.8% water damage, 45.4% window pane condensation, 11.1% mold odor, and 37.5% humid air. All dampness signs were associated with symptoms (ORs from 1.2 to 4.6; P < 0.001), including rhinitis (ORs from 1.4 to 3.2; P < 0.001), and ORs increased by number of dampness signs. The strongest associations were for mold odor (ORs from 2.3 to 4.6) and humid air (ORs from 2.8 to 4.8). Associations were stronger among men and stronger in Beijing as compared to south China. In conclusion, dampness and mold are common in Chinese homes and associated with rhinitis and ocular, throat and dermal symptoms, headache and fatigue. Men can be more sensitive to dampness and health effects of dampness can be stronger in northern China.

The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection.

OBJECTIVES: To develop a patient-reported outcome (PRO) questionnaire for symptoms of Clostridium difficile infection (CDI) following the US Food and Drug Administration PRO guidelines. METHODS: Patients' experiences of CDI symptoms were elicited in open-ended discussions with patients and nurses at five US sites (stage 1). A draft PRO measure was developed after demonstration of concept saturation. Two rounds of cognitive interviews were conducted with patients at three US sites (stage 2), with revision of the draft measure after each round. All patients were 18 years or older, with confirmed CDI. The study was conducted with input from a panel of five CDI experts in Europe and North America. RESULTS: Stage 1 included interviews with 18 patients and supplementary interviews with 6 nurses; 16 additional patients were interviewed in stage 2. Patients were representative of the general CDI population and were diverse in age, sex, and disease severity. Concept saturation was reached in stage 1. Items were organized in a draft conceptual framework with five hypothesized domains: diarrhea, abdominal discomfort, tiredness, lightheadedness, and other symptoms. Stage 2 demonstrated initial content validity of the 13-item draft daily diary (CDI-DaySyms). Participants reported that the questions were clear, relevant, and comprehensive. They were able to use the instructions to complete the diary correctly and considered the 24-hour recall period appropriate. CONCLUSIONS: The CDI-DaySyms captures symptoms relevant to patients undergoing CDI, demonstrating initial content validity. Final content and psychometric validity are being evaluated in a substudy comprising patients from two ongoing international clinical trials (ClinicalTrials.gov identifiers NCT01987895 and NCT01983683).

Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant.

A Case of Silent Q Fever Endocarditis.

Q fever endocarditis is a rare, culture negative endocarditis caused by Coxiella burnetii, a spore-forming gram negative coccobacillus. Presenting symptoms can be very non-specific; thus, diagnosis may be delayed. We present a case of a 65-year-old male patient with history of aortic aneurysm who complained of chronic fatigue. He was found to have aortic valve vegetation on routine echocardiography. Q fever endocarditis was diagnosed based on elevated Q fever serology; there was absence of fever. This case illustrated a rare, under-recognized and atypical manifestation of Q fever endocarditis. We would like to encourage physicians of rural states like South Dakota to remain vigilant when it comes to screening for the suspected cases of Q fever, specifically in cases of unexplained fatigue and valvulopathy.

Severely impaired health status of non-notified Q fever patients leads to an underestimation of the true burden of disease.

Q fever patients are often reported to experience a long-term impaired health status, including fatigue, which can persist for many years. During the large Q fever epidemic in The Netherlands, many patients with a laboratory-confirmed Coxiella burnetii infection were not notified as acute Q fever because they did not fulfil the clinical criteria of the acute Q fever case definition (fever, pneumonia and/or hepatitis). Our study assessed and compared the long-term health status of notified and non-notified Q fever patients at 4 years after onset of illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study included 448 notified and 193 non-notified Q fever patients. The most severely affected subdomain in both patient groups was 'Fatigue' (50·5% of the notified and 54·6% of the non-notified patients had severe fatigue). Long-term health status did not differ significantly between the notified and non-notified patient groups, and patients scored worse on all subdomains compared to a healthy reference group. Our findings suggest that the magnitude of the 2007-2009 Q fever outbreak in The Netherlands was underestimated when only notified patients according to the European Union case definition are considered.

Seroprevalence study of human brucellosis by conventional tests and indigenous indirect enzyme-linked immunosorbent assay.

Brucellosis is one of the most important reemerging zoonoses in many countries. Brucellosis is caused by Gram-negative coccobacillus belonging to genus Brucella. Human brucellosis often makes the diagnosis difficult. The symptoms and clinical signs most commonly reported are fever, fatigue, malaise, chills, sweats headaches, myalgia, arthralgia, and weight loss. Some cases have been presented with only joint pain, lower backache, and involuntary limb movement, burning feet, or ischemic heart attacks. The focus of this work was to develop a highly sensitive and specific indirect ELISA by using smooth lipopolysaccharide antigen of Brucella abortus 99 to detect anti-Brucella antibodies at Project Directorate on Animal Disease Monitoring and Surveillance. Serum samples collected from 652 individuals in whom fever was not the major symptom but the complaint was of joint pain, headache, lower backache, and so forth, were screened by Rose Bengal plate agglutination test (RBPT) and standard tube agglutination test (STAT). Subsequent testing of sera by indigenous indirect ELISA detected 20 samples positive (3.6% seroprevalence), and indirect ELISA was found to be more sensitive than RBPT and STAT. The seroprevalence in South Karnataka was 2.14%, and in North Karnataka it was 0.92%.

Cognitive function, fatigue and Fazekas score in patients with acute neuroborreliosis.

Long-term cognitive problems and fatigue after adequately treated neuroborreliosis has caused uncertainty and debate among patients and health care workers for years. Despite several studies, the prevalence, cause and severity of such complaints are still not clarified. More knowledge about cognitive function, fatigue and MRI findings in the acute phase of neuroborreliosis could possibly contribute to clarification. In the current study, we therefore aimed to address this. Patients with well-characterized acute neuroborreliosis (n = 72) and a matched control group (n = 68) were screened with eight subtests from three different neuropsychological test batteries assessing attention, working memory and processing speed, and with Fatigue Severity Scale. Fazekas score was used to grade white matter hyperintensities on MRI. We found no differences in mean scores on the neuropsychological tests between the groups. The patient group reported significantly higher level of fatigue (Fatigue Severity Scale: 4.8 vs. 2.9, p < .001). There was no significant difference in Fazekas score between the groups. Neuroborreliosis does not seem to affect cognitive functions in the acute state of the disease, while fatigue is common.

Fermented Deer Blood Ameliorates Intense Exercise-Induced Fatigue via Modulating Small Intestine Microbiota and Metabolites in Mice.

Intense and excessive exercise-induced fatigue has become an important health issue and can damage intestinal health. Deer blood, as a food byproduct with nutritional value, has been found to restore physical strength. However, little is known about the antifatigue effect of fermented deer blood (FDB) on intense exercise mice. The purpose of the present study is to investigate the antifatigue effect of FDB, and whether this effect is correlated with the altered small intestinal microbiota and metabolites in exercise mice. In this study, 5-week-old male C57BL/6J mice are given treadmill exercise with or without FDB supplementation (30 and 150 mg/kg/d) for 3 weeks. FDB significantly reduces metabolic byproduct accumulation, liver and intestinal damage, and enhances glycogen storage and antioxidant capacity in intense exercise mice. Moreover, FDB restructures the small intestinal microbiota by increasing the abundance of probiotics and butyric acid producing bacteria and decreasing the abundance of pathogenic bacteria. FDB also regulates the levels of metabolites involved in TCA cycle and amino acid metabolism in urine and small intestine content. Correlation analysis shows that FDB-modulated microbiota is highly associated with its antifatigue effect. FDB may ameliorate fatigue and intestinal injury through targeting small intestinal microbiota.

Associations between the gut microbiome and fatigue in cancer patients.

Fatigue is the most prevalent symptom of cancer and its treatments. Changes in the intestinal microbiome have been identified in chronic fatigue syndrome and other neuropsychiatric disorders, and cancer patients. However, the association between intestinal microbiome and fatigue in patients with advanced cancers has not been evaluated. Understanding the connection between intestinal microbiome and fatigue will provide interventional and therapeutic opportunities to manipulate the microbiome to improve fatigue and other patients' reported outcomes. In this project, we aimed to identify associations between microbiome composition and fatigue in advanced cancer patients. In this cross-sectional observational study at a tertiary cancer care center, we included 88 patients with advanced, metastatic, unresectable cancers who were in a washout period from chemotherapy. We measured fatigue using the MD Anderson Symptom Inventory-Immunotherapy fatigue score, and used 16srRNA to analyze intestinal microbiome. Using correlation analysis we found that Eubacterium hallii was negatively associated with fatigue severity scores (r = - 0.30, p = 0.005), whereas Cosenzaea was positively associated with fatigue scores (r = 0.33, p = 0.0002). We identified microbial species that exhibit distinct composition between high-fatigued and low-fatigued cancer patients. Further studies are warranted to investigate whether modulating the microbiome reduces cancer patients' fatigue severity and improves their quality of life.

Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study.

PURPOSE: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms. METHODS: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24-28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R's vegan package software. RESULTS: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors. CONCLUSION: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.

Linking the gut microbiota to persistent symptoms in survivors of COVID-19 after discharge.

Several follow-up studies have found that COVID-19 (coronavirus disease 2019) patients had persistent symptoms after discharge. Gut microbiota play an important role in human health and immune responses. Therefore, this study investigated the gut microbiota of recovered COVID-19 patients and the correlations between gut microbiota and persistent symptoms after discharge. Stool samples were collected from 15 recovered healthcare workers (HCWs) with COVID-19 at three months after discharge, in addition, stool samples were collected from 14 healthy controls (HCs) to perform 16S rRNA gene sequencing between May and July 2020. Compared with HCs, recovered HCWs had reduced bacterial diversity at three months after discharge, with a significantly higher relative abundance of opportunistic pathogens, and a significantly lower relative abundance of beneficial bacteria. In addition, Escherichia unclassified was positively correlated with persistent symptoms at three months after discharge, including fatigue (r = 0.567, p = 0.028), chest tightness after activity (r = 0.687, p = 0.005), and myalgia (r = 0.523, p = 0.045). Intestinibacter bartlettii was positively correlated with anorexia (r = 0.629, p = 0.012) and fatigue (r = 0.545, p = 0.036). However, Faecalibacterium prausnitzii was negatively correlated with chest tightness after activity (r = -0.591, p = 0.02), and Intestinimonas butyriciproducens was negatively correlated with cough (r = -0.635, p = 0.011). In conclusion, the gut microbiota of recovered HCWs with COVID-19 at three months after discharge was different from that of HCs, and altered gut microbiota was correlated with persistent symptoms after discharge, highlighting that gut microbiota may play an important role in the recovery of patients with COVID-19.

Anti-fatigue property of the oyster polypeptide fraction and its effect on gut microbiota in mice.

We aimed to evaluate the anti-fatigue effects of the oyster polypeptide (OP) fraction and its regulatory effect on the gut microbiota in mice. Our exhaustive swimming experiment showed that the swimming time of the low-, middle- and high-dose groups of the OP fraction was increased by 1.82, 2.18 and 2.44 times compared with the control group, respectively. Besides, the liver glycogen levels of the three groups were increased by 19.3%, 42.02% and 65.07%, while the lactate levels were decreased by 18.85%, 21.18% and 28.74%, respectively. Moreover, administration of the OP fraction upregulated the expressions of PEPCK and AMPK, but downregulated the TNF-α expression. Correlation analysis between the gut microbiota and fatigue-related biochemical indicators showed that Faecalibacterium, Desulfovibri and Intestinibacter were negatively correlated with the swimming time, blood lactate, blood urea nitrogen, liver glycogen and muscle glycogen, while Yaniella and Romboutsia were positively correlated. Therefore, the OP fraction had anti-fatigue effects, and could regulate the abundance of gut microbiota and maintain its balance.

Chronic Brucellosis in Japan.

Human brucellosis, one of the most common zoonoses worldwide, rarely occurs in Japan, and only a few chronic cases have been reported. We herein report the case of a 39-year-old Japanese woman with chronic human brucellosis, considered a Brucella canis infection, that persisted for 19 years. Her medical history and fever pattern suggested chronic brucellosis, and the diagnosis was made based on the results of a serum tube agglutination test (SAT). After undergoing combination therapy with streptomycin and doxycycline, she achieved symptomatic relief and showed negative SAT results. Even in non-endemic areas, chronic brucellosis is an important differential diagnosis in patients with long-term persistent fatigue or a fever.

Kefir Supplementation Modifies Gut Microbiota Composition, Reduces Physical Fatigue, and Improves Exercise Performance in Mice.

The present study evaluated the potential beneficial effect of kefir (KF) against fatigue. Furthermore, the composition of the gut microbiota is related to health benefits in the host; therefore, the study also investigated the effect of KF on the gut microbiota composition. Male ICR mice from four groups (n = 8 per group) were orally administered KF once daily for four weeks at 0, 2.15, 4.31, and 10.76 g/kg/day and were designated as the vehicle, KF-1X, KF-2X, and KF-5X groups, respectively. The gut microbiota was analyzed using 16S rRNA gene sequencing. The results showed a significant clustering of cecum after treatment in the vehicle, KF-1X, KF-2X, and KF-5X groups. The KF-2X and KF-5X groups showed a decreased Firmicutes/Bacteroidetes ratio compared with the vehicle group. In addition, anti-fatigue activity and exercise performance were evaluated on the basis of exhaustive swimming time, forelimb grip strength, and levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) after a swimming exercise. The exhaustive swimming time for the KF-1X, KF-2X, and KF-5X groups was significantly longer than that for the vehicle group, and the forelimb grip strength of the KF-1X, KF-2X, and KF-5X groups was also significantly higher than that of the vehicle group. KF supplementation also decreased serum lactate, ammonia, BUN, and CK levels after the swimming test. However, tissue glycogen content, an important energy source for exercise, increased significantly with KF supplementation. Thus, KF supplementation can alter the gut microbiota composition, improve performance, and combat physical fatigue.

Comparison of Clinical Course and Treatment Outcome for Patients With Early Disseminated or Early Localized Lyme Borreliosis.

Importance: Multiple erythema migrans (MEM) has been suggested as a risk factor for unfavorable antibiotic treatment outcome compared with solitary erythema migrans (EM). However, no direct comparison of early Lyme borreliosis manifested as MEM with solitary EM has been undertaken. Objective: To investigate the potential differences in clinical course and treatment outcome between MEM and solitary EM. Design, Setting, and Participants: This prospective cohort study was conducted from June 1, 2010, to October 31, 2015, at the University Medical Center Ljubljana, Slovenia. Data were analyzed from June 1, 2017, to January 3, 2018. Of the 778 consecutive adult patients with early Lyme borreliosis evaluated, 200 patients with MEM and 403 patients with solitary EM were enrolled. Patients were asked to refer a family member or a friend of similar age (±5 years) without a history of Lyme borreliosis to serve as a control participant. Clinical course and posttreatment outcome of MEM were compared with those of solitary EM. Outcome was assessed at 14 days and at 2, 6, and 12 months after enrollment. At each visit, patients completed a written questionnaire about their symptoms; controls completed the same questionnaire. Nonspecific symptoms reported by patients and controls without a history of Lyme borreliosis were compared. Main Outcomes and Measures: The proportion of patients with incomplete response at 12 months after enrollment and the associated 2-sided 95% CI for the difference between MEM and solitary EM were estimated using the normal approximation with continuity correction. Results: A total of 200 patients with MEM and 403 patients with solitary EM were included. Among the 200 patients with MEM, 94 (47.0%) were males and 106 (53.0%) were females, with a median (interquartile range [IQR]) age of 47 (35-58) years. Among the 403 patients with solitary EM, 182 (45.2%) were males and 221 (54.8%) were females, with a median (IQR) age of 55 (42-62) years. Patients with MEM reported Lyme borreliosis-associated constitutional symptoms at enrollment more often than those with solitary EM (93 [46.5%]; 95% CI, 39.4-53.7 vs 96 [23.8%]; 95% CI, 19.7-28.3; P < .001). During the initial 6 months after treatment, the proportion of patients with incomplete response was higher in the MEM group than in the solitary EM group (14 days: 62 of 193 [32.1%] vs 72 of 391 [18.4%]; P < .001; 2 months: 38 of 193 [19.7%] vs 55 of 394 [14.0%]; P = .28; 6 months: 29 of 182 [15.9%] vs 31 of 359 [8.6%]; P = .02). However, at the 12-month visit, the outcome was comparable: 10 of 170 (5.9%) patients with MEM vs 20 of 308 (6.5%) patients with solitary EM showed incomplete response (-0.6; 95% CI, -5.5 to 4.3; P = .95). The frequency of nonspecific symptoms in patients was similar to that in controls. Conclusions and Relevance: The long-term outcome at 12 months after treatment was comparable, regardless of dissemination. Follow-up of at least 12 months after treatment is thus recommended for future studies that investigate post-Lyme borreliosis symptoms.

Elevation of Candida IgG antibodies in patients with medically unexplained symptoms.

BACKGROUND: The hypothesis that an immunologic reaction to Candida yeasts, present in the gastrointestinal tract, causes a diffuse collection of multisystem symptoms is not generally accepted within conventional medicine. A questionnaire, the Fungus Related Disease Questionnaire (FRDQ-7), was previously developed and used to identify patients for a randomized, placebo-controlled trial of the nonabsorbed antifungal drug nystatin. Nystatin was superior to placebo in relieving these symptoms. This provides some support for the hypotheses that underpin the "Candida syndrome". AIM: The aim of this study was to identify a population with a high (>9) FRDQ-7 score and symptom-free controls and, subsequently, to explore the relationship between FRDQ-7 scores and Candida immunoglobulin (Ig)A, IgG, and IgM levels. DESIGN: This was a case-controlled study. METHODS: Santelmann has suggested that the FRDQ-7 describes people with Candida syndrome if the FRDQ-7 score is >9; 35 patients with medically unexplained symptoms, between ages 18 and 64, were selected for the study if they scored > 9 on the FRDQ-7 questionnaire. Serum Candida IgA, IgG, and IgM measurements were undertaken both for this group and a group of 45 healthy age- and gender-matched controls, and the Ig concentrations were compared. RESULTS: Candida IgG concentration was significantly higher in the noncontrol group than in the control group (p < 0.001). No significant difference was found for Candida IgA or IgM concentrations. CONCLUSIONS: Further studies are required to identify whether there is a causal link for the elevation of serum IgG found in this subgroup of patients with increased FRDQ-7 scores, or whether these two observations are parallel manifestations of a common underlying disorder.

Treatment of aspergillosis in an immunocompetent patient: a multidisciplinary approach.

CASE STUDY: P.J. was a 69-year-old woman who was referred to a large cancer center for an evaluation of brain and lung masses presumed to be cancerous lesions. During the three months before the referral, P.J. had experienced a gradual 40 lb weight loss, shortness of breath with exertion, chest pain, lip tremor, edema and progressive weakening of lower extremities, overall fatigue, and increasing balance and gait disturbances. Her diagnostic workup revealed aspergillosis in her lungs and brain. This case study reports the process of differentiating between cancer and fungal disease, antifungal treatment modalities used, and the multidisciplinary management approach used in the care of P.J.